Inadequate specimen contrast, the effects of dehydration and beam damage limit application of the electron microscope to problems in biopolymer structure. The proposed research will continue to develop high resolution specimen-preparation methods, applying new or recently-improved techniques to systems of biological and/or clinical interest. The latter include: cell surface glycoproteins, muscle proteins, blood proteins (including immune-system components) and bronchial mucins. The proposed research is divided into three parts: (a) Optimization of specimen preparation by improvement in fine-grain metal replication techniques developed in this laboratory; (b) A study of the degree and effects of hydration of small globular proteins by comparison of measurements on both air-dried and lyophilized electron microscope preparations with parameters measured in solution; (c) Applications to specific problems of biological and potential clinical importance will include: (1) Mapping of structural features by means of group- specific markers (such as lectins or IgG, complexed with the glycosidic side chains of glycoproteins. Subjects of mapping experiments will include epiglycanin (a mammary tumor cell surface glycoprotein which has been related to metastatic potential), fibrinogen, myosin, complement component Clq. (2) Determination of size, shape and conformation of other macromolecular systems including bronchial mucins, fibronectin (cold insoluble globulin), complement component Clq (with particular reference to the evolutionary origin of this structurally distinctive macromolecule), and hamster female protein (apparently a new member of the 'pentraxin' group which includes cross reactive protein and the P-component of amyloid deposits).